An increased dietary intake of saturated fat and cholesterol has been associated with elevations in plasma cholesterol and low density lipoprotein (LDL) cholesterol levels, decreased bleeding time, enhanced platelet aggregation, alterations in immune function, and an increased risk of developing premature coronary artery disease (CAD). An increased dietary intake of polyunsaturated fats and/or dietary saturated fat restriction appears to decrease some of these adverse associations. Moreover polyunsaturated fats are mainly essential fatty acids and their daily nutritional requirements have not been established. The aims of this research are to carry out well controlled diet studies on the effects of: 1) altering the dietary content of linoleic acid (0%, 2%. 6% and 8% of calories) or of its derivative gamma linolenic acid (0% and 2% of calories), 2) altering the dietary content of linolenic acid (0%, 0.3%, 2%, and 4%) or its derivatives eicosapentaenoic acid and docosahexaenoic acid (0% and 2%) of calories; 3) testing the long term effects (1 year) of a diet containing 10% saturated fat, 100 mg cholesterol/1000 calories, and 10% polyunsaturated fat and a diet containing 5% saturated fat, 60 mg cholesterol/1000 calories, and 10% polyunsaturated fat. Diet studies 1 and 2 will be carried out in 10 normolipidemic subjects each and study 3 will be carried out in 20 normolipidemic subjects, 10 subjects with familial hypoalphalipo proteinemia, and 10 subjects with familial combined hyperlipidemia. Parameters to be examined will include plasma lipoprotein lipid content, apolipoproteins A-I, A-II, B, and E, LDL and HDL subclasses, VLDL and LDL apoB-100 and HDL apoA-I kinetics, plasma lipoprotein alterations in response to a defined fat meal (1 gm/kg of fat), platelet thromboxane B2 (a measure of platelet aggregation), bleeding time, blood pressure, delayed hypersensitivity response, peripheral blood mononuclear cell mitogenic response to T and B cell mitogens and lymphokine formation. The objectives of the project are to define optimal dietary intakes of essential fatty acids and their derivatives, saturated fats, monounsaturated fats, and cholesterol in normal and dyslipidemic humans in terms of improving parameters associated with premature CAD (elevated LDL, decreased HDL, increased blood pressure, and increased bleeding time).